Effects of sodium butyrate on the intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier

Abstract

Objective To explore the effects of different concentrations of sodium butyrate on a Caco-2 cell monolayer model of intestinal barrier and to investigate the potential influence of p38 MAPK on this process.Methods The Caco-2 cell monolayer model of intestinal barrier was established via cell culture,which was further divided into 3 groups including the control group,the sodium butyrate groups with different concentrations (2 mmol/L,5 mmol/L,and 8 mmol/L)) and the sodium butyrate (5 mmol/L) + SB203580(20μmol/L,p38MAPK specific inhibitor)group.After 72 hours of culture,the transepithelial electrical resistance (TER) and the barrier permeability by testing the concentration of inulin-FITC were detected.The surface of Caco-2 cells was observed by electronic scanning microscopy.Results After 3 weeks of culture,monolayer Caco-2 cells formed the intestinal epithelial cell barrier model.After incubation of sodium butyrate (2 mmol/L) on Caco-2 cell monolayers for 72 h,the TER was increased to (467.65 ± 7.41) Ω·cm2 compared to (417.58 ± 6.29)Ω·cm2 in the control group (P＜0.05).After incubation of sodium butyrate (5 mmol/L or 8 mmol/L) on Caco-2 cells monolayer for 72 h,the TERs were (113.87 ± 20.27)Ω· cm2 and (58.60 ± 29.02)Ω· cm2,which were both significantly lower than those in the control group (P＜0.05).The inulin-FITC permeability was (11.08± 1.04)％ and (16.01 ± 1.56)％ in these 2 groups (P＜0.05,compared to the control group).However,the TER and permeability of the 5 mmol/L sodium butyrate + 20 μmol/L SB203580 group were (395.17 ± 9.97)Ω·cm2 and (7.19 ± 0.97)％ (both P＜0.05,compared to those in the 5 mmol/L sodium butyrate group).The electronic microscopy revealed that the surface of the Caco-2 cells,which were treated with 0 mmol/L and 2 mmol/L sodium butyrate,was connected tightly without cell float.The surface impairment and cell float of Caco-2 cell monolayers were increased in a concentration-dependent fashion.Compared to that in the 5 mmol/L sodium butyrate group,the cell loss in the 5 mmol/L sodium butyrate + 20 μmol/L SB203580 group were significantly decreased.Conclusions The low concentration of sodium butyrate may be beneficial in promoting intestinal barrier functions,whereas excessive sodium butyrate may disrupt normal intestinal barrier.And p38MAPK specific inhibitor SB203580 could decrease the damage of the intestinal barrier function induced by sodium butyrate. Key words: Fatty acids, volatile; Intestinal mucosa; Mitogen-activated protein kinases